We have demonstrated that exogenous antigen antibody reactions (EAR), administered via implanted cannulae to the perifornical hypothalamus in the rat, cause changes in pharmacologically induced eating and drinking behaviors. Since immune complexes, e.g. human serum albumin (HSA) and rabbit anti HSA, are able to initiate the complement (C') cascade, focal production of anaphylatoxins (AT) C3a and C5a are considered likely mediators of the interference with neuropharmacologic systems. Tests show that crude rat C5a mimics the effect of norepinephrine (NE) injected into the site and C3a (1 nmole) enhances the behavioral activation induced by adrenergic and cholinergic agonists at the same site. The objective of the experiments described in this proposal are to confirm the neuropharacological correlates of EAR and AT activities and to explore the possible mechanisms of action. 1. We will establish the dependence of EAR effect on activation by C', a) by testing its activity in rats decomplemented by cobra venom factor, and b) by using non C' -fixing F(ab')2 fragments of the antibody IgG. 2. We will determine the psychopharmacological correlates the C3a and C5a at several brain sites differentially enriched of adrenergic, cholinergic and dopaminergic receptors by dose response and receptor blocker studies. 3. We will determine the distribution by brain region and cell types of binding sites for C3a and C5a. 125I-ATs will be used for autoradiographic localization and for quantitative binding to tissue punches, cultured neural cells and synaptosomes. Double label immunoflourescence will be used with anti AT and antineural call markers to associate AT sites with cell types. 4. We will determine any relationships between AT sites and transmitter receptors by competitive radioligand binding to tissue punches and synaptosomes. 5. We will test the hypothesis that AT acts in the CNS to trigger release of transmitter, analogous to their action on mast cells and basophils in other tissue. Release from punches and synaptosomes will be assessed by 3H-transmitter uptake/release methods and by HPLC with electrochemical detection. Alternative mechanisms of reuptake inhibition will be tested. The frequency of neuropsychiatric disorders asociated with autoimmune diseases, especially CNS-lupus, suggests that animal models relating immune phenomena to specific neural functions can be useful.